tbuckley/cabot-search huggingface dataset:
Inversion polymorphism in a complete human genome assembly
Authors: David Porubsky, William T. Harvey, Allison N. Rozanski, Jana Ebler, Wolfram Höps, Hufsah Ashraf, Patrick Hasenfeld, Benedict Paten, Ashley D. Sanders, Tobias Marschall, Jan O. Korbel, Evan E. Eichler
Journal: Genome biology (2023)

The telomere-to-telomere (T2T) complete human reference has significantly improved our ability to characterize genome structural variation. To understand its impact on inversion polymorphisms, we remapped data from 41 genomes against the T2T reference genome and compared it to the GRCh38 reference. We find a ~ 21% increase in sensitivity improving mapping of 63 inversions on the T2T reference. We identify 26 misorientations within GRCh38 and show that the T2T reference is three times more likely to represent the correct orientation of the major human allele. Analysis of 10 additional samples reveals novel rare inversions at chromosomes 15q25.2, 16p11.2, 16q22.1-23.1, and 22q11.21.
SNV-FEAST: microbial source tracking with single nucleotide variants
Authors: Leah Briscoe, Eran Halperin, Nandita R. Garud
Journal: Genome biology (2023)

Abstract Elucidating the sources of a microbiome can provide insight into the ecological dynamics responsible for the formation of these communities. Source tracking approaches to date leverage species abundance information; however, single nucleotide variants (SNVs) may be more informative because of their high specificity to certain sources. To overcome the computational burden of utilizing all SNVs for a given sample, we introduce a novel method to identify signature SNVs for source tracking. Signature SNVs used as input into a previously designed source tracking algorithm, FEAST, can more accurately estimate contributions than species and provide novel insights, demonstrated in three case studies.
Health-related Quality of Life in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Multi-center UK Study
Authors: Margarita Papatheodoridi, Giada Pallini, Guruprasad Aithal, Hong Kai Lim, Jeremy Cobbold, Maria Corina Plaz Torres, Marta Guerrero Misas, John Ryan, Jeremy Tomlinson, Michael Allison, Louise Longworth, Emmanuel A. Tsochatzis
Journal: Clinical Gastroenterology and Hepatology (2023)

It is unclear whether health-related quality of life (HRQoL) is impaired in patients with nonalcoholic fatty liver disease (NAFLD) without advanced fibrosis and how this compares with the general population. We aimed to assess HRQoL in patients with NAFLD in comparison to the general population and any associations of fibrosis severity and metabolic comorbidities with impairments in HRQoL.
DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection
Authors: Mikkel H. Christensen, Simon O. Drue, Mads H. Rasmussen, Amanda Frydendahl, Iben Lyskjær, Christina Demuth, Jesper Nors, Kåre A. Gotschalck, Lene H. Iversen, Claus L. Andersen, Jakob Skou Pedersen
Journal: Genome biology (2023)

Abstract Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions. Using DREAMS, we develop statistical methods for variant calling (DREAMS-vc) and cancer detection (DREAMS-cc). For evaluation, we generate deep targeted NGS data of matching tumor and plasma DNA from 85 colorectal cancer patients. The DREAMS approach performs better than state-of-the-art methods for variant calling and cancer detection.
Clarithromycin-Resistant Genotypes and Eradication of <i>Helicobacter pylori</i>
Authors: Vincenzo De Francesco, Marcella Margiotta, Angelo Zullo, Cesare Hassan, Laura Troiani, Osvaldo Burattini, Francesca Stella, Alfredo Di Leo, Francesco Russo, Stefania Marangi, Rosa Monno, Vincenzo Stoppino, Sergio Morini, Carmine Panella, Enzo Ierardi
Journal: Annals of Internal Medicine (2006)

Background: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. Objective: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. Design: Post hoc subgroup study from a multicenter, randomized trial. Setting: Two hospitals in central and southern Italy between January and December 2001. Patients: 156 patients with H. pylori infection. Measurements: Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. Intervention: 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. Results: Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). Limitations: The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (€70 per patient). Conclusions: The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.
Evoked Potentials in Clinical Medicine
Authors: Keith H. Chiappa, Allan H. Ropper
Journal: New England Journal of Medicine (1982)

ONE of the most useful techniques in modern clinical neurophysiology is the recording of evoked potentials. An evoked potential (EP) is an electrical manifestation of the brain's response to an external stimulus. For example, the visual EP produced by the flash of a strobe light can often be seen as a wave in the occipital region in the electroencephalogram. Most EPs, however, cannot be seen in routine electroencephalographic recordings because of their very low amplitudes (0.1 to 20 μV) and their admixture with background brain-wave activity and artifacts.The EP must be extracted from background activity by the technique of . . .
All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study
Authors: Alane Izu, Marta C Nunes, Fatima Solomon, Vicky Baillie, Natali Serafin, Charl Verwey, David P Moore, Marius Laubscher, Musawenkosi Ncube, Courtney Olwagen, Ziyaad Dangor, Shabir A Madhi
Journal: The Lancet Infectious Diseases (2023)
Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study
Authors: Caige Huang, Yue Wei, Vincent K C Yan, Xuxiao Ye, Wei Kang, Hei Hang Edmund Yiu, Jessica J P Shami, Benjamin J Cowling, Man Li Tse, David J Castle, Celine S L Chui, Francisco T T Lai, Xue Li, Eric Y F Wan, Carlos K H Wong, Joseph F Hayes, Wing Chung Chang, Albert K K Chung, Chak Sing Lau, Ian C K Wong, Esther W Chan
Journal: The Lancet Psychiatry (2023)
Distinct Insulin Physiology Trajectories in Euglycemic Pregnancy and Gestational Diabetes Mellitus
Authors: Tanayott Thaweethai, Zainab Soetan, Kaitlyn James, Jose C. Florez, Camille E. Powe
Journal: Diabetes Care (2023)

To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM).Participants underwent oral glucose tolerance tests at ≤15 weeks' gestation (early pregnancy), 24-32 weeks' gestation (mid-late pregnancy), and 6-24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify β-cell compensation for insulin resistance.Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (β = -0.20, P < 0.001) and substantially in mid-late pregnancy (β = -0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (β = 0.16, P < 0.001) and mid-late pregnancy (β = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (β = 215, P = 0.04) but not mid-late pregnancy (β = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (β = -0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61-0.79], area under the curve with PIP index 0.87 [95% CI 0.80-0.93]).β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM.
In persons with constipation or IBS-C, kiwifruit vs. psyllium increased spontaneous bowel movements
Authors: Blake J. Purtle, Brooks D. Cash
Journal: Annals of Internal Medicine (2023)

Source Citation Gearry R, Fukudo S, Barbara G, et al. Consumption of 2 green kiwifruits daily improves constipation and abdominal comfort—results of an international multicenter randomized controlled trial. Am J Gastroenterol. 9 Jan 2023. [Epub ahead of print]. 36537785
In prediabetes, oral vitamin D reduces progression to new-onset diabetes
Authors: Darren Lau
Journal: Annals of Internal Medicine (2023)

Source Citation Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med. 2023;176:355-363. 36745886
Tecovirimat Treatment of People With HIV During the 2022 Mpox Outbreak
Authors: Jacob McLean, Kate Stoeckle, Simian Huang, Jonathan Berardi, Brett Gray, Marshall J. Glesby, Jason Zucker
Journal: Annals of Internal Medicine (2023)

Background: The recent mpox outbreak has disproportionately affected people with HIV (PWH) and resulted in the first widespread use of the novel antiviral tecovirimat. Whether treatment outcomes differ between PWH and those without HIV is unknown. Objective: To compare the clinical presentation and treatment outcomes of PWH and HIV-negative persons with mpox virus (MPXV) infection treated with tecovirimat. Design: Retrospective cohort study of patients treated with tecovirimat for confirmed MPXV infection from June to August 2022. Setting: Two academic medical centers in New York City. Participants: The study included 196 persons treated with tecovirimat from 20 June to 29 August 2022. Of 154 testing positive for MPXV, 72 were PWH and 4 had a CD4 count lower than 0.20 × 109 cells/L. Measurements: Patient demographic characteristics, clinical presentation, treatment outcomes, and safety data for tecovirimat. Results: Indications for tecovirimat treatment were similar between the PWH and HIV-negative groups. Four participants had serious adverse events; none were attributed to tecovirimat. Three of these 4 participants had HIV infection, and 2 had CD4 counts less than 0.20 × 109 cells/L. Twenty-two percent of participants had nonsevere adverse effects. Groups had similar rates of hospitalization, indications for treatment, and co-occurring infections, but PWH had fewer days from symptom onset to treatment (7.5 vs. 10). There was no difference in treatment outcomes, including days to improvement or rate of persistent symptoms. Limitation: Patients with mpox who were not treated with tecovirimat were not followed routinely and therefore lacked comparable outcome data, limiting evaluation of efficacy. Conclusion: In our cohort of patients treated with tecovirimat for severe mpox, HIV status did not seem to affect treatment outcomes. Primary Funding Source: National Institutes of Health.
In type 2 MI, the T2-risk score predicted death or MI at 1 y
Authors: Dominic L. Raco
Journal: Annals of Internal Medicine (2023)

Taggart C, Monterrubio-Gómez K, Roos A, et al. Improving risk stratification for patients with type 2 myocardial infarction. J Am Coll Cardiol. 2023;81:156-168. 36631210.
Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
Authors: Claire N. Harrison, Jyoti Nangalia, Rebecca Boucher, Aimee Jackson, Christina Yap, Jennifer O'Sullivan, Sonia Fox, Isaak Ailts, Amylou C. Dueck, Holly L. Geyer, Ruben A. Mesa, William G. Dunn, Eugene Nadezhdin, Natalia Curto-Garcia, Anna Green, Bridget Wilkins, Jason Coppell, John Laurie, Mamta Garg, Joanne Ewing, Steven Knapper, Josephine Crowe, Frederick Chen, Ioannis Koutsavlis, Anna Godfrey, Siamak Arami, Mark Drummond, Jennifer Byrne, Fiona Clark, Carolyn Mead-Harvey, Elizabeth Joanna Baxter, Mary Frances McMullin, Adam J. Mead
Journal: Journal of Clinical Oncology (2023)

PURPOSE Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P &lt; .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
Annals On Call - Opioids and the Treatment of Chronic Pain
Authors: Robert M. Centor, Leah J. Leisch
Journal: Annals of Internal Medicine (2023)

Web ExclusivesMay 2023Annals On Call - Opioids and the Treatment of Chronic PainFREERobert M. Centor, MD and Leah J. Leisch, MDRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author and Leah J. Leisch, MDUniversity of Alabama at Birmingham Medical Center, Birmingham, Alabama (L.J.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A22-0009 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses current recommendations regarding the use of opioids for the treatment of chronic pain with Dr. Leah Leisch.Annals articles discussed include...The Use of Opioids in the Management of Chronic Pain: Synopsis of the 2022 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline: https://www.acpjournals.org/doi/10.7326/M22-2917About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Robert M. Centor, MD; Leah J. Leisch, MDAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)University of Alabama at Birmingham Medical Center, Birmingham, Alabama (L.J.L.)Disclosures: All relevant financial relationships have been mitigated. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=A22-0009.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures.This article was published at Annals.org on 2 May 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Use of Opioids in the Management of Chronic Pain: Synopsis of the 2022 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline Friedhelm Sandbrink , Jennifer L. Murphy , Melanie Johansson , Juli L. Olson , Ellen Edens , Jamie Clinton-Lont , James Sall , and Christopher Spevak , for the VA/DoD Guideline Development Group Metrics Current IssueMay 2023Volume 176, Issue 5 ePublished: 2 May 2023 Issue Published: May 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...
Disparities in Prevalence and Trend of Methamphetamine-Associated Cardiomyopathy in the United States
Authors: Md. Shenuarin Bhuiyan, Abu Saleh Mosa Faisal, Maamannan Venkataraj, Nicholas E. Goeders, Steven R. Bailey, Steven A. Conrad, John A. Vanchiere, A. Wayne Orr, Christopher G. Kevil, Mohammad Alfrad Nobel Bhuiyan
Journal: Journal of the American College of Cardiology (2023)
A Series of Abnormal ECGs: Are They Benign or Sinister?
Authors: Hongdan Duan, Chuan-Hai Zhang
Journal: Circulation (2023)

A 36-year-old man presented to the hospital for routine physical examination.He was otherwise asymptomatic.His vital signs and laboratory results were normal.An ECG was obtained (shown in Figure 1A), after which two more consecutive ECGs were obtained (shown in Figure 1B and1C).What do these ECG changes represent?What is the mechanism behind them?Please turn the page to read the diagnosis.
In outpatients with mild to moderate COVID-19, low-dose fluvoxamine did not reduce time to sustained recovery
Authors: Jeremy Clark, Steven Y.C. Tong
Journal: Annals of Internal Medicine (2023)

Source Citation McCarthy MW, Naggie S, Boulware DR, et al. Effect of fluvoxamine vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2023;329:296-305. 36633838
In mechanically ventilated patients at nutritional risk, high protein did not reduce time to discharge alive
Authors: Rahul Nanchal
Journal: Annals of Internal Medicine (2023)

Source Citation Heyland DK, Patel J, Compher C, et al; EFFORT Protein Trial team. The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial. Lancet. 2023;401:568-576. 36708732
In limb or pelvic fracture, aspirin was noninferior to enoxaparin for reducing all-cause death
Authors: Michael Griffin, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2023)

Source Citation Major Extremity Trauma Research Consortium (METRC); O’Toole RV, Stein DM, O’Hara NN, et al. Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture. N Engl J Med. 2023;388:203-213. 36652352
Prioritizing Quality Measures in Acute Stroke Care
Authors: Jinyi Zhu, Hooman Kamel, Ajay Gupta, Alvin I. Mushlin, Nicolas A. Menzies, Thomas A. Gaziano, Meredith B. Rosenthal, Ankur Pandya
Journal: Annals of Internal Medicine (2023)

The American Heart Association and American Stroke Association (AHA/ASA) endorsed 15 process measures for acute ischemic stroke (AIS) to improve the quality of care. Identifying the highest-value measures could reduce the administrative burden of quality measure adoption while retaining much of the value of quality improvement. To prioritize AHA/ASA-endorsed quality measures for AIS on the basis of health impact and cost-effectiveness. Individual-based stroke simulation model. Published literature. U.S. patients with incident AIS. Lifetime. Health care sector. Current versus complete (100%) implementation at the population level of quality measures endorsed by the AHA/ASA with sufficient clinical evidence (10 of 15). Life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and incremental net health benefits. Discounted life-years gained from complete implementation would range from 472 (tobacco use counseling) to 34 688 (early carotid imaging) for an annual AIS patient cohort. All AIS quality measures were cost-saving or highly cost-effective by AHA standards (<$50 000 per QALY for high-value care). Early carotid imaging and intravenous tissue plasminogen activator contributed the largest fraction of the total potential value of quality improvement (measured as incremental net health benefit), accounting for 72% of the total value. The top 5 quality measures accounted for 92% of the total potential value. A web-based user interface allows for context-specific sensitivity and scenario analyses. Correlations between quality measures were not incorporated. Substantial variation exists in the potential net benefit of quality improvement across AIS quality measures. Benefits were highly concentrated among 5 of 10 measures assessed. Our results can help providers and payers set priorities for quality improvement efforts and value-based payments in AIS care. National Institute of Neurological Disorders and Stroke.
In adults with VTE who received anticoagulants for ≥3 mo, VTE-PREDICT predicted recurrence and bleeding at up to 5 y
Authors: Richard H. White
Journal: Annals of Internal Medicine (2023)

Source Citation de Winter MA, Büller HR, Carrier M, et al; VTE-PREDICT study group. Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score. Eur Heart J. 2023;44:1231-1244. 36648242